U of T researchers are leading the way in determining a genetic basis for obsessive-compulsive disorder (OCD), a psychiatric illness that affects 2.5 per cent of the general population—approximately 750,000 Canadians.
The disorder is characterized by a number of symptoms. Typically, individuals affected by OCD have intrusive and unwanted thoughts, images or impulses (obsessions) that provoke anxiety. In response, these individuals engage in various forms of repetitive or ritualistic behaviour, called compulsions, to alleviate their discomfort.
“Among the most common obsessions are fears regarding dirt or germs and doubt about being responsible for harm,” said Dr. Peggy Richter, staff psychiatrist in the anxiety disorders clinic at the Centre for Addiction and Mental Health (CAMH), and assistant professor in the faculty of medicine at U of T.
“The most common compulsions are washing and cleaning rituals,” Richter said. Sufferers may wash excessively in order to alleviate the anxiety they experience from the feeling their body is unclean. They often avoid touching common objects such as doorknobs.
They might do everything in multiples of a certain number to prevent a dreaded event, or check things over and over because of doubt, such as repeatedly making sure that doors are locked, or endlessly checking the stove to be certain the elements are shut off. If they drive, they may also circle back to make sure they haven’t hurt anyone.
Made popular by characters such as Monica on Friends and Melvin in As Good As It Gets, OCD has only been well-recognized and understood in the last 20 to 30 years. “Previously it was wrongly dismissed as a rare condition, and was given relatively little attention,” said Richter.
Internationally, CAMH is one of the leaders investigating the genetic predisposition for OCD. Richter and her team study individuals with the disease and their relatives. Blood samples are taken from subjects for DNA analysis to try and determine what genes contribute to OCD.
“One of the most effective and well-known ways of identifying the genes involved in a disorder is to look at frequency of variance of those genes, or alleles, and compare people who have the disorder to people who don’t have it,” Richter said.
A gene provides the code for a specific protein essential to bodily structure or function. All individuals have the same basic genes, but different people often have different versions of a particular gene. “That kind of variability is what is informative and necessary for us to be able to make any interpretation,” said Richter. When compared to the rest of the population, the frequency of a certain allele may be significantly higher among individuals with a particular disorder.
In the case of OCD, the gene of interest is called 5HT1Dbeta. A variant of this gene, called the G861 allele, has been found to occur more often among individuals diagnosed with the illness.
5HT1Dbeta codes for the receptor (a site on the surface of neurons in the brain) that binds the neurotransmitter serotonin. Like most neurotransmitters, serotonin is found in many cells in different areas of the brain, transmitting signals from one cell to another.
“Abnormalities in serotonin neurotransmission have been associated with all kinds of problems, including OCD, other anxiety disorders, mood disorders, suicide risk, impulsivity, and attention deficit [disorder],” said Richter.
However, it is not yet clear what these abnormalities are. “There are so many different places where you could have a problem that would result in a change in function,” Richter said. “We don’t understand specifically what the problem is.”
Researchers linked 5HT1Dbeta to OCD after observing that drugs that increase serotonin neurotransmission are effective for individuals who suffer from OCD. Examples are Prozac, Anafranil and Luvox.
Richter is now waiting for other researchers to establish the same high frequency of the G861 allele in OCD sufferers. Once this is done, Richter hopes to better understand how changes in this gene actually contribute to the risk for the disorder.
“One way would be to look at the people with this particular variant in more detail compared to people who don’t have it, and see if we can determine other associated differences,” she said.
Unlike many psychiatric disorders, there is little evidence to suggest OCD has environmental factors that cause the disease. OCD is most effectively treated by medication and behaviour therapy. Behaviour therapy consists of exposure and ritual prevention, where individuals confront the things or situations that provoke anxiety, but refrain from carrying out their usual compulsions. Over time, their obsessions begin to fade and the urge to perform compulsions subsides.
For some individuals, however, neither form of treatment is effective. By identifying and understanding OCD genes, doctors to hope to tailor individualized responses to treatments.
